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The interaction between anti-PF4 antibodies and anticoagulants in vaccine-induced thrombotic thrombocytopenia.
Singh, Anurag; Toma, Filip; Uzun, Günalp; Wagner, Teresa R; Pelzl, Lisann; Zlamal, Jan; Freytag, Verena; Weich, Karoline; Nowak-Harnau, Stefanie; Rothbauer, Ulrich; Althaus, Karina; Bakchoul, Tamam.
  • Singh A; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Toma F; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Uzun G; Center for Clinical Transfusion Medicine Tuebingen, Tuebingen, Germany.
  • Wagner TR; Pharmaceutical Biotechnology, Eberhard Karls University, Tuebingen, Germany; and.
  • Pelzl L; Natural and Medical Sciences Institute (NMI) at the University of Tuebingen, Reutlingen, Germany.
  • Zlamal J; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Freytag V; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Weich K; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Nowak-Harnau S; Institute for Clinical and Experimental Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany.
  • Rothbauer U; Center for Clinical Transfusion Medicine Tuebingen, Tuebingen, Germany.
  • Althaus K; Pharmaceutical Biotechnology, Eberhard Karls University, Tuebingen, Germany; and.
  • Bakchoul T; Natural and Medical Sciences Institute (NMI) at the University of Tuebingen, Reutlingen, Germany.
Blood ; 139(23): 3430-3438, 2022 06 09.
Article in English | MEDLINE | ID: covidwho-1759684
ABSTRACT
Life-threatening thrombotic events at unusual sites have been reported after vector-based vaccinations against severe acute respiratory syndrome coronavirus 2. This phenomenon is now termed vaccine-induced immune thrombotic thrombocytopenia (VITT). The pathophysiology of VITT is similar to that of heparin-induced thrombocytopenia (HIT) and is associated with platelet-activating antibodies (Abs) against platelet factor 4 (PF4). Therefore, current guidelines suggest nonheparin anticoagulants to treat VITT patients. In this study, we investigated the interactions of heparin, danaparoid, fondaparinux, and argatroban with VITT-Ab/PF4 complexes using an ex vivo model for thrombus formation as well as in vitro assays to analyze Ab binding and platelet activation. We found that immunoglobulin Gs (IgGs) from VITT patients induce increased adherent platelets/thrombus formation in comparison with IgGs from healthy controls. In this ex vivo flow-based model, the procoagulant activity of VITT IgGs was effectively inhibited with danaparoid and argatroban but also by heparin. Interestingly, heparin and danaparoid not only inhibited IgG binding to PF4 but were also able to effectively dissociate the preformed PF4/IgG complexes. Fondaparinux reduced the in vitro generation of procoagulant platelets and thrombus formation; however, it did not affect platelet aggregation. In contrast, argatroban showed no effect on procoagulant platelets and aggregation but significantly inhibited VITT-mediated thrombus formation. Taken together, our data indicate that negatively charged anticoagulants can disrupt VITT-Ab/PF4 interactions, which might serve as an approach to reduce Ab-mediated complications in VITT. Our results should be confirmed, however, in a clinical setting before a recommendation regarding the selection of anticoagulants in VITT patients could be made.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombocytopenia / Thrombosis / COVID-19 Vaccines / Anticoagulants Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Blood Year: 2022 Document Type: Article Affiliation country: Blood.2021013839

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombocytopenia / Thrombosis / COVID-19 Vaccines / Anticoagulants Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Blood Year: 2022 Document Type: Article Affiliation country: Blood.2021013839